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Interleukin‐7 induces T cell proliferation in the absence of Erk/MAP kinase activity
Author(s) -
Crawley James B.,
Willcocks Joannie,
Foxwell Brian M. J.
Publication year - 1996
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830261125
Subject(s) - mapk/erk pathway , biology , microbiology and biotechnology , phosphorylation , mitogen activated protein kinase , tyrosine phosphorylation , kinase , tyrosine kinase , signal transduction
Abstract Interleukin (IL)‐7 and IL‐2 are important lymphoproliferative cytokines which both use the γc chain as part of their respective receptors. To learn more of their signaling mechanisms a comparison was made of the patterns of intracellular tyrosine phosphorylated proteins induced by these cytokines in the murine T cell line, CT6. Several similarities were revealed in the tyrosine phosphorylated proteins induced. However, a notable subset of proteins of mainly < 60 kDa were only phosphorylated by IL‐2. Characterization of the two most prominent bands of this subset, pp54 and pp42, revealed these to contain Shc and p42 MAP/Erk kinase, respectively. Further studies confirmed that IL‐7 was unable to induce the phosphorylation of either the p44 MAP/Erk or p42 MAP/Erk or activation of the kinases. Shc is involved in activation of p21 ras , a key event in the signaling cascade, via p72 raf and MEK, leading to MAP/Erk kinase (MAPK) activation. These data indicate that this pathway is not utilized by IL‐7 and may not, therefore, be essential for cytokine‐driven T cell proliferation. This possibility was supported by studies with the MEK inhibitor PD098059, which had no selective effect on CT6 proliferation induced by IL‐2 as compared with IL‐7, although the drug completely inhibited MAP/Erk phosphorylation induced by IL‐2.